Synthesis and anti-proliferative effect of substituted imidazo[4,5-b]pyridine compounds

Abstract

This invention provides for compounds, compositions, and methods that involve anti-proliferative and anti-neoplastic activity in cancer cells. In particular, a series of benzimidazole, purine, imidazopyridine, and imidazopyrizine compounds having selected substitution patterns are disclosed, and the activity of various subject compounds is demonstrated. In particular, the disclosure provides for substituted imidazo[4,5-b]pyridine compounds having the general formula their salts, pharmaceutical compositions, and methods of treatment using the subject compounds and compositions.

1. A compound having the formula: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically-acceptable salt thereof, wherein
 G is selected from 
 
       
         
           
           
               
               
           
         
       
       and
 X is selected from hydrogen, a halide, an alkyl having up to 10 carbon atoms which is optionally substituted with at least one halide, and an alkoxide having up to 10 carbon atoms which is optionally substituted with at least one halide; 
 Z is selected from CH 2 , NH, O, and S; 
 Q is selected from CH 2 , NH, O, and S; 
 n is selected from 1, 2, and 3; and 
 X D  is selected from 
 
       
         
           
           
               
               
           
         
       
       and Y is O or NH. 
     
     
       2. A compound according to  claim 1 , wherein
 G is selected from and 
 
       
         
           
           
               
               
           
         
       
       and
 X is selected from hydrogen, a halide, an alkyl having up to 10 carbon atoms which is optionally substituted with at least one halide, and an alkoxide having up to 10 carbon atoms which is optionally substituted with at least one halide. 
 
     
     
       3. A compound according to  claim 2 , wherein X is selected from CH 3 , C(CH 3 ) 3 , and OCH 3 . 
     
     
       4. A compound according to  claim 1  having the formula: 
       
         
           
           
               
               
           
         
       
       wherein
 X is selected from hydrogen, a halide, an alkyl having up to 10 carbon atoms which is optionally substituted with at least one halide, and an alkoxide having up to 10 carbon atoms which is optionally substituted with at least one halide; and 
 X D  is selected from 
 
       
         
           
           
               
               
           
         
       
       and Y is O or NH. 
     
     
       5. A compound according to  claim 1 , wherein
 G is selected from 
 
       
         
           
           
               
               
           
         
         X is selected from hydrogen, a halide, an alkyl having up to 10 carbon atoms which is optionally substituted with at least one halide, and an alkoxide having up to 10 carbon atoms which is optionally substituted with at least one halide; 
         Z is selected from CH 2 , NH, O, and S; 
         Q is selected from CH 2 , NH, O, and S; and 
         n is selected from 1, 2, and 3. 
       
     
     
       6. A compound according to  claim 1 , wherein
 G is selected from 
 
       
         
           
           
               
               
           
         
       
       and
 n is selected from 1, 2, and 3. 
 
     
     
       7. A compound according to  claim 1 , wherein:
 G is selected from 
 
       
         
           
           
               
               
           
         
         Z is selected from CH 2 , NH, O, and S; and 
         Q is selected from CH 2 , NH, O, and S. 
       
     
     
       8. A compound according to  claim 1  having the formula: 
       
         
           
           
               
               
           
         
       
       wherein
 G is selected from 
 
       
         
           
           
               
               
           
         
         X is selected from hydrogen, a halide, an alkyl having up to 10 carbon atoms which is optionally substituted with at least one halide, and an alkoxide having up to 10 carbon atoms which is optionally substituted with at least one halide; 
         Z is selected from CH 2 , NH, O, and S; 
         Q is selected from CH 2 , NH, O, and S; and 
         n is selected from 1, 2, and 3. 
       
     
     
       9. A compound according to  claim 1  having the formula: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       wherein
 X D  is selected from 
 
       
         
           
           
               
               
           
         
       
       and Y is O or NH. 
     
     
       10. A compound according to  claim 1  having the formula: 
       
         
           
           
               
               
           
         
       
       wherein
 G is selected from 
 
       
         
           
           
               
               
           
         
       
     
     
       11. A compound according to  claim 1  having the formula: 
       
         
           
           
               
               
           
         
       
     
     
       12. A compound according to  claim 1  having the formula: 
       
         
           
           
               
               
           
         
       
       wherein
 X is selected from CH 3 , C(CH 3 ) 3 , and OCH 3 . 
 
     
     
       13. A compound according to  claim 1  having the formula: 
       
         
           
           
               
               
           
         
       
       wherein
 Q is selected from CH 2 , NH, O, and S. 
 
     
     
       14. A compound according to  claim 1  having the formula: 
       
         
           
           
               
               
           
         
       
     
     
       15. A compound according to  claim 1  having the formula: 
       
         
           
           
               
               
           
         
       
     
     
       16. A compound according to  claim 1  having the formula: 
       
         
           
           
               
               
           
         
       
     
     
       17. A compound according to  claim 1  having the formula: 
       
         
           
           
               
               
           
         
       
     
     
       18. A compound according to  claim 1  having the formula: 
       
         
           
           
               
               
           
         
       
     
     
       19. A pharmaceutically-acceptable salt of a compound according to  claim 1 . 
     
     
       20. A pharmaceutical composition comprising a therapeutically-effective amount of at least one compound according to  claim 1  or a pharmaceutically-acceptable salt thereof, and a pharmaceutically-acceptable carrier.